SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-10-3313. This Article Full Text (PDF) All Versions of this Article: 2002-10-3313v1 101/10/3953    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Belcher, J. D Articles by Vercellotti, G. M Search for Related Content PubMed PubMed Citation Articles by Belcher, J. D Articles by Vercellotti, G. M Social Bookmarking                   What's this? Submitted November 5, 2002 Accepted January 2, 2003 Transgenic sickle mice have vascular inflammation John D Belcher*, Christopher J Bryant, Julia Nguyen, Paul R Bowlin, Miroslaw C Kielbik, John C Bischof, Robert P Hebbel, and Gregory M Vercellotti Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA * Corresponding author; email: belcher{at}umn.edu. Inflammation may play an essential role in vaso-occlusion in sickle cell disease. Sickle patients have high white counts and elevated levels of serum C-reactive protein (CRP), cytokines and adhesion molecules. In addition, circulating endothelial cells, leukocytes and platelets are activated. We examined four transgenic mouse models expressing human alpha and sickle beta globin genes to determine if they mimic the inflammatory response seen in patients. These mouse models are designated "NY-S", "Berk-SAntilles", "NY-S/SAntilles" (NY-S X Berk-SAntilles), and "Berk-S." The mean white counts were elevated 1.4- to 2.1-fold (p0.01) in the Berk-SAntilles, NY-S/SAntilles, and Berk-S mice, but not in the NY-S mice compared to normal. Serum amyloid P-component (SAP), an acute phase response protein with 60-70% sequence homology to CRP, was elevated 8.5- to 12.1-fold (p0.001) in transgenic sickle mice. Similarly, serum interleukin-6 (IL-6) was elevated 1.6- to 1.9-fold (p0.05). Western blots, confirming immuno-histochemical staining, showed vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM) and platelet-endothelial cell adhesion molecule (PECAM) were upregulated 3- to 5-fold (p0.05) in the lungs of sickle mice. Ribonuclease protection assays (RPA) demonstrated VCAM mRNA also was elevated in sickle mice 1.2- to 1.4-fold (p0.01). Nuclear factor kappa B (NF-B), a transcription factor critical for the inflammatory response, was elevated 1.9-fold (p0.006) in NY-S sickle mouse lungs. We conclude that transgenic sickle mice are good models to study vascular inflammation and the potential benefit of anti-inflammatory therapies to prevent vaso-occlusion in sickle cell disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. D. Beckman, J. D. Belcher, J. V. Vineyard, C. Chen, J. Nguyen, M. O. Nwaneri, M. G. O'Sullivan, E. Gulbahce, R. P. Hebbel, and G. M. Vercellotti Inhaled carbon monoxide reduces leukocytosis in a murine model of sickle cell disease Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1243 - H1253. [Abstract] [Full Text] [PDF] K. L. Wallace, M. A. Marshall, S. I. Ramos, J. A. Lannigan, J. J. Field, R. M. Strieter, and J. Linden NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-{gamma} and CXCR3 chemokines Blood, July 16, 2009; 114(3): 667 - 676. [Abstract] [Full Text] [PDF] G. J. Kato and M. T. Gladwin Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy JAMA, December 10, 2008; 300(22): 2638 - 2646. [Abstract] [Full Text] [PDF] M. T. Gladwin and E. Vichinsky Pulmonary Complications of Sickle Cell Disease N. Engl. J. Med., November 20, 2008; 359(21): 2254 - 2265. [Full Text] [PDF] S. D. Nandedkar, T. R. Feroah, W. Hutchins, D. Weihrauch, K. S. Konduri, J. Wang, R. C. Strunk, M. R. DeBaun, C. A. Hillery, and K. A. Pritchard Histopathology of experimentally induced asthma in a murine model of sickle cell disease Blood, September 15, 2008; 112(6): 2529 - 2538. [Abstract] [Full Text] [PDF] F. Vinchi, S. Gastaldi, L. Silengo, F. Altruda, and E. Tolosano Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload Am. J. Pathol., July 1, 2008; 173(1): 289 - 299. [Abstract] [Full Text] [PDF] D. R. Archer, J. K. Stiles, G. W. Newman, A. Quarshie, L. L. Hsu, P. Sayavongsa, J. Perry, E. M. Jackson, and J. M. Hibbert C-Reactive Protein and Interleukin-6 Are Decreased in Transgenic Sickle Cell Mice Fed a High Protein Diet J. Nutr., June 1, 2008; 138(6): 1148 - 1152. [Abstract] [Full Text] [PDF] L. L. Hsu, H. C. Champion, S. A. Campbell-Lee, T. J. Bivalacqua, E. A. Manci, B. A. Diwan, D. M. Schimel, A. E. Cochard, X. Wang, A. N. Schechter, et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability Blood, April 1, 2007; 109(7): 3088 - 3098. [Abstract] [Full Text] [PDF] D. K. Kaul, X.-d. Liu, X. Zhang, T. Mankelow, S. Parsons, F. Spring, X. An, N. Mohandas, D. Anstee, and J. A. Chasis Peptides based on {alpha}V-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation Am J Physiol Cell Physiol, November 1, 2006; 291(5): C922 - C930. [Abstract] [Full Text] [PDF] D. K. Kaul, X.-d. Liu, X. Zhang, L. Ma, C. J. C. Hsia, and R. L. Nagel Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H167 - H175. [Abstract] [Full Text] [PDF] D. K. Sokol, Demao Chen, M. R. Farlow, D. W. Dunn, B. Maloney, J. A. Zimmer, and D. K. Lahiri High Levels of Alzheimer Beta-Amyloid Precursor Protein (APP) in Children With Severely Autistic Behavior and Aggression J Child Neurol, June 1, 2006; 21(6): 444 - 449. [Abstract] [PDF] E. A. Manci, C. A. Hillery, C. A. Bodian, Z. G. Zhang, G. A. Lutty, and B. S. Coller Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease Blood, February 15, 2006; 107(4): 1651 - 1658. [Abstract] [Full Text] [PDF] J. D. Belcher, H. Mahaseth, T. E. Welch, A. E. Vilback, K. M. Sonbol, V. S. Kalambur, P. R. Bowlin, J. C. Bischof, R. P. Hebbel, and G. M. Vercellotti Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2715 - H2725. [Abstract] [Full Text] [PDF] K. A. Nath, J. P. Grande, A. J. Croatt, E. Frank, N. M. Caplice, R. P. Hebbel, and Z. S. Katusic Transgenic Sickle Mice Are Markedly Sensitive to Renal Ischemia-Reperfusion Injury Am. J. Pathol., April 1, 2005; 166(4): 963 - 972. [Abstract] [Full Text] [PDF] J. M. Hibbert, L. L. Hsu, S. J. Bhathena, I. Irune, B. Sarfo, M. S. Creary, B. E. Gee, A. I. Mohamed, I. D. Buchanan, A. Al-Mahmoud, et al. Proinflammatory Cytokines and the Hypermetabolism of Children with Sickle Cell Disease Experimental Biology and Medicine, January 1, 2005; 230(1): 68 - 74. [Abstract] [Full Text] [PDF] K. A. Blackwell, J. P. Sorenson, D. M. Richardson, L. A. Smith, O. Suda, K. Nath, and Z. S. Katusic Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2448 - H2453. [Abstract] [Full Text] [PDF] A. Solovey, R. Kollander, A. Shet, L. C. Milbauer, S. Choong, A. Panoskaltsis-Mortari, B. R. Blazar, R. J. Kelm Jr, and R. P. Hebbel Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin Blood, August 1, 2004; 104(3): 840 - 846. [Abstract] [Full Text] [PDF] M. L. Jison, P. J. Munson, J. J. Barb, A. F. Suffredini, S. Talwar, C. Logun, N. Raghavachari, J. H. Beigel, J. H. Shelhamer, R. L. Danner, et al. Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease Blood, July 1, 2004; 104(1): 270 - 280. [Abstract] [Full Text] [PDF] J. H. Schwartz, C. A. White, and B. A. Freeman Do we kNOw how HSP90 and eNOS mediate lung injury in sickle cell disease? Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L701 - L704. [Full Text] [PDF] A. Greenough Sickle Cell Disease--Pulmonary Complications and a Proinflammatory State? Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 663 - 665. [Full Text] [PDF] J. D. Holtzclaw, D. Jack, S. M. Aguayo, J. R. Eckman, J. Roman, and L. L. Hsu Enhanced Pulmonary and Systemic Response to Endotoxin in Transgenic Sickle Mice Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 687 - 695. [Abstract] [Full Text] [PDF] A. Turhan, P. Jenab, P. Bruhns, J. V. Ravetch, B. S. Coller, and P. S. Frenette Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes Blood, March 15, 2004; 103(6): 2397 - 2400. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020